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A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors


Phase 2
18 Years
N/A
Not Enrolling
Both
Gastrinoma, Glucagonoma, Insulinoma, Islet Cell Carcinoma, Pancreatic Polypeptide Tumor, Recurrent Islet Cell Carcinoma, Somatostatinoma

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Trial Information

A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors


PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) associated with temozolomide alone or
temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

SECONDARY OBJECTIVES:

I. To evaluate response rates (RR) associated with temozolomide alone or temozolomide and
capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

II. To evaluate overall survival (OS) associated with temozolomide alone or temozolomide and
capecitabine in patients with advanced pancreatic neuroendocrine tumors.

III. To evaluate the toxicity associated with temozolomide alone or temozolomide and
capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

IV. To evaluate the usefulness of methyl guanine methyltransferase (MGMT) status (by
immunohistochemistry [IHC] and promoter methylation) for predicting response in pancreatic
neuroendocrine tumor patients treated with either temozolomide or temozolomide and
capecitabine.

V. To bank radiology images for evaluation of quality, reproducibility, and compliance with
computed tomography (CT) methodology.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment
repeats every 28 days for up to 13 courses in the absence of disease progression or
unacceptable toxicity.

ARM B: Patients receive capecitabine PO twice daily (BID) on days 1-14 and temozolomide PO
QD on days 10-14. Treatment repeats every 28 days for up to 13 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years,
and then every 6 months for 3 years.


Inclusion Criteria:



- Patient must have histologically or pathologically confirmed locally unresectable or
metastatic low or intermediate grade pancreatic neuroendocrine tumor, excluding small
cell carcinoma

- Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease
must be obtained =< 4 weeks prior to randomization and must be acquired by
multiphasic CT or contrast magnetic resonance imaging (MRI)

- Randomization must occur =< 12 months of last documented disease progression

- Patient must not have received prior temozolomide, dacarbazine (DTIC), or
capecitabine, or 5-FU (fluorouracil) therapy

- Prior everolimus or sunitinib therapy is allowed, so long as it was discontinued >= 4
weeks prior to randomization

- Concurrent somatostatin analogues are allowed provided that patients

- Have been on stable doses for 8 weeks and

- Have documented disease progression on that dose

- Patients may not be receiving any other investigational agents while on study
treatment

- Patients may not be receiving Coumadin while on treatment; other anticoagulants are
allowed

- Leukocytes >= 3,000/mm^3

- Absolute neutrophil count >= 1,500/mm^3

- Hemoglobin >= 9 g/dL

- Platelets >= 100,000/mm^3

- Total bilirubin =< institutional upper limit of normal (ULN) or =< 1.5 X
institutional ULN (if the patient has liver metastases)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT])
=< 3 X institutional ULN or (=< 5 X institutional ULN if the patient has liver
metastases)

- Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Patient must have life expectancy >= 12 weeks

- Patients with either clinically apparent central nervous system metastases or
carcinomatous meningitis are ineligible

- Patients must NOT have active or uncontrolled infection or serious medical or
psychiatric illness

- Patients must NOT have history of allergic reactions attributed to compounds of
similar chemical or biologic composition to temozolomide or capecitabine

- Patient must NOT have absorption issues that would limit the ability to absorb study
agents

- Patients with a history of the following within =< 12 months of study entry are not
eligible:

- Arterial thromboembolic events

- Unstable angina

- Myocardial Infarction

- Patients with symptomatic peripheral vascular disease are not eligible

- Patients must NOT have previous or concurrent malignancy; exceptions are made for
patients who meet any of the following conditions:

- Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ OR

- Prior malignancy completely excised or removed and patient has been continuously
disease free for > 5 years

- Women must not be pregnant or breast-feeding due to potential harm to fetus from
temozolomide and/or capecitabine; all females of childbearing potential must have a
blood test or urine study within =< 2 weeks prior to randomization to rule out
pregnancy; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)

- Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for the duration of their participation in the study; should a woman
become pregnant while participating in this study, she should inform her treating
physician immediately; if a man impregnates a woman while participating in this
study, he should inform his treating physician immediately

- Patient must be able to swallow pills

- Patient must be able to tolerate CT or MR imaging including contrast agents as
required for their treatment and the protocol

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PFS

Outcome Description:

There will be two log-rank tests conducted, an interim analysis at 76% information and a final analysis at 100% information (105 PFS events), projected to occur at 3 years from the start of accrual. The overall type I error will be controlled using an O'Brien-Fleming boundary function. If the repeated two-sided 95% confidence interval on the hazard ratio does not contain the target alternative hazard ratio of 0.64, consideration will be given to declaring the study negative and reporting the results.

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Pamela Kunz

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eastern Cooperative Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

E2211

NCT ID:

NCT01824875

Start Date:

December 2012

Completion Date:

Related Keywords:

  • Gastrinoma
  • Glucagonoma
  • Insulinoma
  • Islet Cell Carcinoma
  • Pancreatic Polypeptide Tumor
  • Recurrent Islet Cell Carcinoma
  • Somatostatinoma
  • Carcinoma
  • Gastrinoma
  • Zollinger-Ellison Syndrome
  • Glucagonoma
  • Insulinoma
  • Somatostatinoma
  • Neuroendocrine Tumors
  • Adenoma, Islet Cell
  • Carcinoma, Islet Cell

Name

Location

Eastern Cooperative Oncology GroupBoston, Massachusetts  02215